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Updated: Jun 20, 2026

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
Published on: September 28, 2018
ITAM-derived phosphopeptide-containing dendrimers as multivalent ligands for Syk tandem SH2 domain
Joeri Kuil1, Hilbert M Branderhorst, Roland J Pieters
1Utrecht Institute for Pharmaceutical Sciences, Medicinal Chemistry & Chemical Biology, PO Box 80082, Utrecht, 3508 TB, Netherlands.
Abstract:
Spleen tyrosine kinase (Syk) is activated when its tandem SH2 domain (tSH2) binds to a diphosphorylated ITAM motif of e.g. the FcepsilonRI receptor. In this divalent interaction each SH2 domain binds to a phosphotyrosine-containing tetrapeptide motif in ITAM. One of those tetrapeptide sequences was synthesized and conjugated to dendrimers via 'click' chemistry to create a series of functional phosphopeptide-containing dendrimers ranging from a monovalent to an octavalent dendrimer. The affinity of the functionalized dendrimers for Syk tSH2 has been assayed in SPR competition experiments. Both the tetra- and octavalent dendrimer had an affinity in the high nanomolar range, which is approximately 100-fold enhanced compared to the monovalent tetrapeptide, indicating a multivalency effect.
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